In Duchenne Muscular Dystrophy, the absence of dystrophin leads to a dramatic decrease of the Dystrophin-Associated Protein Complex (DAPC) required to connect intracellular actin microfilaments to the extracellular matrix (Matsumura et al., 1994; Ervasti et al., 2008). As a consequence, the muscle fibers become more sensitive to mechanical damage leading to muscle degeneration, chronic inflammatory response and increase in fibrosis, all of which exacerbate the dystrophic phenotype. As a consequence, alterations of many cellular processes occur. At present, several therapeutic strategies have been successfully tested in animal models of muscular dystrophies and some of them are currently entering clinical trials. Among the most promising approaches, exon skipping allows the rescue of dystrophin synthesis through the production of a shorter but functional mRNA (Denti et al., 2006, 2008).
The authors identify a miRNA (miR-31), particularly abundant in dystrophic regenerating fibers that represses dystrophin expression. They also show that by means of sequestering miR-31 or of protecting its target sequence on the dystrophin 3′UTR, an increase of translation of dystrophin is obtained.